ArticleNature communications2024
Acid-exposed and hypoxic cancer cells do not overlap but are interdependent for unsaturated fatty acid resources.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Efficacy, safety, and biomarker analysis of neoadjuvant camrelizumab plus apatinib as a chemotherapy-free strategy for early-stage triple-negative breast cancer: a phase II study.Breast cancer research and treatment · 2026Trial
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Fatty Acid Metabolism and Hypoxia in the Tumor Microenvironment: Metabolic Adaptation and Clinical Potential in Colorectal Cancer.Biomedicines · 2026Review
- Stearoyl-CoA desaturase 1 integrates tissue-specific oncogenic pathways into a pan-cancer ferroptosis resistance program.Cell death & disease · 2026Review
- Targeting the lipid desaturation network in cancer: from metabolic plasticity to precision therapeutics.Journal of experimental & clinical cancer research : CR · 2026Review
- Deconstructing cancer in 3D: models, mechanisms, and personalized solutions.Molecular cancer · 2026Review
- CA9 targets ITGB1 to accelerate the progression of colorectal cancer by promoting the neutrophil extracellular traps formation.Journal of translational medicine · 2026Article
- Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis.Nature cell biology · 2026Article
- Acidosis Forces Fatty Acid Uptake and Metabolism in Cancer Cells Regardless of Genotype.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Macrophage fatty acid metabolism under chronic hypoxia shapes γδ T cell recruitment via CCL22.iScience · 2025Article
Corrections and comments
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells in acidic tumor regions are aggressive and a key therapeutic target, but distinguishing between acid-exposed and hypoxic cells is challenging. Here, we use carbonic anhydrase 9 (CA9) antibodies to mark acidic areas in both hypoxic and respiring tumor areas, along with an HRE-GFP reporter for hypoxia, to isolate distinct cell populations from 3D tumor spheroids. Transcriptomic analysis of CA9-positive, hypoxia-negative cells highlights enriched fatty acid desaturase activity. Inhibiting or silencing stearoyl-CoA desaturase-1 (SCD1) induces ferroptosis in CA9-positive acidic cancer cells and delays mouse tumor growth, an effect enhanced by omega-3 fatty acid supplementation. Using acid-exposed cancer cells and patient-derived tumor organoids, we show that SCD1 inhibition increases acidic cancer cell reliance on external mono-unsaturated fatty acids, depriving hypoxic cells of essential resources. This bystander effect provides unbiased evidence for a lack of full overlap between hypoxic and acidic tumor compartments, highlighting a rationale for targeting desaturase activity in cancer.
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